Determinants involved in subtype-specific functions of rat trace amine-associated receptors 1 and 4.

British journal of pharmacology

PubMedID: 23072560

Stäubert C, Bohnekamp J, Schöneberg T. Determinants involved in subtype-specific functions of rat trace amine-associated receptors 1 and 4. Br J Pharmacol. 2013;168(5):1266-78.
AIMS
The trace amine-associated receptor (Taar) family displays high species- and subtype-specific pharmacology. Several trace amines such as ß-phenylethylamine (ß-PEA), p-tyramine and tryptamine are agonists at TA(1) but poorly activate rat and mouse Taar4.

PRINCIPAL RESULTS
Using rat TA(1) and Taar4 chimera, we identified determinants in transmembrane helices 3 and 6, which, when replaced by the corresponding portion of rat TA(1) , can rescue cell surface expression of rat Taar4. When expressed at the cell surface, rat Taar4 pharmacology was very similar to that of TA(1) and coupled to the Ga(s) -protein/AC pathway. Our data suggest that binding pockets of Taar for surrogate agonists overlap between paralogs.

CONCLUSIONS
This implicates that the repertoire of Taar ensures functional redundancy, tissue- and cell-specific expression and/or different downstream signalling rather than different agonist specificity.